[Application of Asn-Gly-Arg sequence based cyclic peptides for targeted tumor therapy].

Abstract

The in vivo antitumor effect of two NGR sequence containing peptide-daunomycin conjugates was studied on CD13+ Kaposi's sarcoma s.c. tumor model on SCID mice, and on orthotopically developed CD13- HT-29 colon adenocarcinoma SCID mouse model. Both tumor types were positive for integrins. Significant tumor growth inhibition was observed on both tumor types by the treatment with the conjugates (Dau=Aoa-GFLGK(cyclo[KNGRE]-GG)-NH2 (1) and Dau=Aoa-GFLGK(cyclo[NleNGRE]-GG)-NH2 (2)). KS conjugate 1 with rather stable construct was more potent in tumor growth inhibition that might be explained by the CD13 receptor recognition of NGR sequence. In contrast, conjugate 2 that has propensity to rearrange isoAsp derivative showed significantly higher inhibition on CD13- HT-29 tumor model that is related to the integrin binding of isoDGR sequence. Next to the low toxic side effect of the conjugates in comparison with the free daunomycin, the positive efficiency of the conjugates was detected by the lower proliferation index and lower neovascularization of the tumor tissue.